Figure 1.

Fatigue determinants in Fabry disease. Several mechanisms are potentially involved in the fatigability experienced by Fabry patients including cardiopulmonary alterations, kidney failure, anhidrosis, cognitive impairment, and skeletal muscle disarrangement. Specifically, primarily skeletal muscle alterations that can strongly impact physical performance have been described: (i) inflammation can potentially drive muscle atrophy; (ii) endothelial dysfunction can induce altered muscle vascularization with impaired oxygen and nutrient supply; (iii) putative mitochondrial dysfunction can induce bioenergetic alterations. The metabolic stress triggers the release of specific mitomiRs which can drive a maladaptive metabolic reprogramming of skeletal muscle. The illustration has been created by Biorender (License number EW26AUO200).